It was recently demonstrated that imaging of brain tumors by relative cerebral blood volume (CBV) maps reconstructed from dynamic magnetic resonance (MR) data provide similar diagnostic information compared to positron emission tomography (PET) or 201Tl single-photon emission computerized tomography (201Tl-SPECT) scans. The authors used relative CBV mapping for routine follow-up evaluation of patients with brain tumors and compared its sensitivity to diagnostic MR imaging, 201Tl-SPECT and clinical assessment. Fifty-nine patients were prospectively followed using 191 concomitant studies of dual section relative CBV maps, MR imaging, 201Tl-SPECT, and neurological evaluations. Studies were repeated every 2 to 3 months (median three evaluations/patient). The relative CBV maps were graded as relative CBV 0 to 4, where Grades 3 and 4 are indicative of proliferating tumors (four = rapid leak). There were 44 high-grade and 15 low-grade tumors followed during treatment. During the follow-up period a change in relative CBV grade was observed in 56% of the patients, revealing an increasing grade in 72% of them. The rapid leak phenomenon was detected in 35% of all studies and in 81% of those with a worsening relative CBV grade. Tumor progression was detected earlier by relative CBV maps as follows: earlier than MR imaging in 32% of the studies (earlier by a median of 4.5 months; p < 0.01); earlier than 201Tl-SPECT in 63% (median 4.5 months; p < 0.01), and earlier than clinical assessment in 55% (median 6 months; p < 0.01). In 82% of studies with positive MR imaging but negative 201Tl-SPECT, the lesions were smaller than 1.5 cm. The relative CBV maps clearly delineated the appearance of rapid leak in these lesions. Routine use of relative CBV maps that can be implemented on any high-field MR unit and added to the regular MR evaluation provides useful functional information in patients with brain tumors. When used as an adjunct follow-up evaluation it proved more sensitive than the other modalities for early prediction of tumor growth. It is very sensitive to small regional changes, unlike functional imaging such as PET or SPECT scans. Based on previous experience with 76 regional CBV studies, the authors conclude that regional CBV mapping correlates with active tumor and it may separate enhancing scar and radiation injury from infiltrative tumor. A new effect named the rapid leak phenomenon was also observed; this phenomenon, as identified on the regional CBV maps, correlates with high malignancy.